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J Cell Biol. 2009 November 16; 187(4): 444.
PMCID: PMC2779234
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Sizing up the ER stress response

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ER membranes (green) expand in response to ER stress (right).

Schuck et al. report that, when it comes to counteracting ER stress, size matters.

When stressful conditions impair protein folding in the ER, the cell responds by producing more ER-resident chaperone proteins and by increasing the organelle's size. ER membrane expansion involves ramping up lipid biosynthesis, but it's unclear whether the growth has a direct role in alleviating stress, or whether it simply provides more space to accommodate the additional protein-folding machinery.

Schuck et al. found that budding yeast need Ino2 and Ino4, two transcription factors that induce a range of lipid synthesis enzymes, to expand their ER in response to stress. ER enlargement also relied on key components of the signaling pathway that coordinates the cell's unfolded protein response, but yeast could bypass this requirement if Ino2 and Ino4 were constitutively activated. Cells lacking Ino2 were more sensitive to stress, whereas Ino2 activation and subsequent ER growth offered a degree of protection to yeast unable to increase their chaperone levels, indicating that membrane expansion alone can alleviate ER stress.

Most of the extended ER is in the form of membrane sheets, but converting these to tubules by overexpressing the reticulon protein Rtn1 didn't change the protective effects of membrane expansion. This suggests that size, rather than shape, is the key factor, says lead author Sebastian Schuck. One possibility is that unfolded proteins are diluted in a larger ER, making them less likely to collide and aggregate.

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